title: Assessment of predictive markers of response to neoadjuvant chemotherapy in breast cancer.
abstract: OBJECTIVE
  To identify the predictive markers associated with chemotherapy sensitivity, especially those producing pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer.
  
  
  METHODS
  Core needle biopsy of 50 locally advanced breast cancer patients was analysed for histopathology, grade, oestrogen receptor, progesterone receptor, HER2, Ki-67, p53, Bcl-2, and BAX before starting NACT. This was correlated with response to NACT using Response Evaluation Criteria in Solid Tumours criteria.
  
  
  RESULTS
  The mean tumour reduction rate per chemotherapy cycle was significantly higher in BAX-positive (p = 0.01) and Bcl-2-negative (p = 0.04) tumours. BAX expression significantly (p = 0.043) correlated with a response of an at least 30% reduction in tumour size post-NACT on multivariate analysis. A significant relationship was seen between loss of Bcl-2 expression and pCR on univariate (p = 0.048) analysis. Overall, all of the above 12 parameters had 30.4% and 28.5% success in predicting clinical complete response and pCR, respectively, by the Cox and Snell formula.
  
  
  CONCLUSIONS
  Of all parameters examined, only the apoptosis-related genes (Bcl-2 and BAX) seemed to exert some influence on the response to NACT, and neither by itself was sufficient to predict pCR; however, 50 patients is not sufficient to simultaneously analyse several predictive markers.
authors.affiliation: Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Mallika
authors.initials: M
authors.lastname: Tewari
authors.forename: Satyajit
authors.initials: S
authors.lastname: Pradhan
authors.forename: Usha
authors.initials: U
authors.lastname: Singh
authors.forename: Taj Bali
authors.initials: TB
authors.lastname: Singh
authors.forename: Hari Shankar
authors.initials: HS
authors.lastname: Shukla
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018567:Breast Neoplasms, Male / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C508053:ERBB2 protein, human